A 30 yard strike from Robert Koren gave Hull the points at the KC Stadium as Town slipped to a third successive defeat.
The Tigers' midfielder arrowed a drive past Brian Murphy 15 minutes from time in a game of few chances, with Jason Scotland and substitute Tamas Priskin going closest for Blues.
Town made four changes to the side that went down at home to Barnsley last week, Murphy replacing Marton Fulop in goal, with David Norris and Grant Leadbitter returning to midfield. Darren O'Dea came in at left-back for his first game since undergoing knee surgery six weeks ago.
Scotland was denied by Vitor Mannone inside the first two minutes after Jake Livermore and Jack Colback linked up, while at the other end John Bostock fired over from 20 yards.
Murphy showed good awareness to clear the danger from Ian Ashbee's delivery, then Livermore's pass almost sent Scotland in on goal in a cagey opening to the game.
Damien Delaney, up against his former club, cleared from Koren's cross as the defences of both teams held the upperhand and it took until the 40th minute for a real effort at goal, Kevin Kilbane heading against the bar from James Harper's cross.
Less than a minute later, Ashbee hit the woodwork with a 20 yard strike, Murphy beaten all the way.
Scotland had an opening inside the first 30 seconds of the restart, taking advantage of sloppy Hull defending but he failed to trouble Mannone in the Tigers' goal.
Hull responded with Koren's shot beaten away by Tommy Smith, Murphy then quickly off his line as the former West Brom midfielder burst into the Blues' box.
Hull made a double change just before the hour, Nick Barmby and Mark Cullen on for Kilbane and Bostock. Blues also making a substitution with Tamas Priskin replacing Scotland.
The Hungarian international was immediately in the action, helping to set up Carlos Edwards who powered a strike that threatened Mannone's goal.
Norris got his body in the way of former Town loanee Liam Rosenior's shot as Nigel Pearson's side searched for an opening in the Blues' defence, Colback almost getting on the end of Leadbitter's cross as Town likewise looked for the advantage.
Hull made a third change with Nobby Solano on for Garcia and Town making a second swap with Jaime Peters replacing Livermore for the final 25 minutes.
Veterans Solano and Barmby had a hand in the breakthrough for the Tigers 15 minutes from time, the duo combining to release Koren 30 yards out and he beat Murphy with a terrific strike.
Blues immediately made a final change, Connor Wickham coming on for Norris - the new England U21 international looking to get in on Peters' cross.
Priskin lost out in a 50-50 with Mannone as he threatened an equaliser, the striker then blazing a shot just wide.
Ashbee picked up the first yellow card of the game for a foul on Colback, then Wickham appeared to be pulled back inside the box - Blues players making their protests known to the officials.
Smith did well to combat the threat of Mark Cullen as Hull broke in added on time - Barmby then went through in a one on one but the former England international couldn't beat Murphy.
O'Dea was booked in the last seconds after a melee in the Hull box following a corner but the points slipped away for Town with one final blast of the whistle.
Hull: Mannone, Rosenior, Zayatte, Gerrard, Dawson, Bostock (Barmby 57), Harper, Ashbee, Koren, Kilbane (Cullen 57), Garcia (Solano 66). Subs not used: Cairney, Cooper, Devitt, Duke. Booked: Ashbee.Town: Murphy, Eastman, Delaney, Smith, O'Dea, Edwards, Norris (Wickham 78), Leadbitter, Livermore (Peters 67), Colback, Scotland (Priskin 58). Subs not used: Fulop, Townsend, Brown, Murray. Booked: O'Dea.